Guanine nucleotide-binding proteins (G proteins) are a family of signal transducers which are found associated with the plasma membrane within eukaryotic cells, and which act to relay signals from certain cell-surface receptor molecules (G-coupled receptors) to effectors in the plasma membrane. G proteins are functional dimers consisting of .alpha. (G.alpha.) and .beta..gamma. (G.beta..gamma.) subunits (Stryer et al., Ann. Rev. Cell Biol. 2:391-419, 1986). Some presently-known members of this family include the G proteins termed G.sub.o1, G.sub.o2, G.sub.i1, G.sub.i2, G.sub.i3, G.sub.s, G.sub.q, and the G.sub.q -related family which presently includes G.sub.11, G.sub.12, G.sub.13, G.sub.14, G.sub.15, and G.sub.16 (see, e.g., Kaziro, "Structures of the Genes Coding for the .alpha. Subunits of G Proteins", Chapter 11 in ADP--ribosylating Toxins and G Proteins (Moss, J., and Vaughan, M. eds.) pp189-206, American Society for Microbiology, Washington, D.C., 1988). Each individual G protein is characterized as such by the particular .alpha. subunit species (e.g., G.sub.o1 .alpha., G.sub.o2 .alpha., etc.) which forms the .alpha. portion of the dimeric protein. In their unstimulated condition, G proteins are .alpha..beta..gamma. forms bound to guanosine diphosphate (GDP); upon receptor stimulation they dissociate into GTP-bound Go and nucleotide-free G.beta..gamma., leading to the activation of the next effector protein in the cascade. In at least one case, this activation results in the opening of a calcium channel in the membrane, thereby increasing calcium influx in the cell (Kojima et al., Biochem. Biophys. Res. Commun. 154:9-19, 1988; Matsunaga et al., Am. J. Physiol. 255:C442-C446, 1988).
Okamoto et al. (Cell 62:709-717, 1990; hereby incorporated by reference) identified the region of one G-coupled receptor protein (insulin-like growth factor II receptor, or IGF-IIR) which directly interacts with and activates G.sub.i2 ; this region of IGF-IIR is sometimes referred to as that receptor's "couplone". A synthetic peptide (termed "Peptide 14") having a sequence identical to that of IGF-IIR's couplone was found to bind to and activate G.sub.i2. Studies on synthetic variants of this peptide permitted Okamoto et al. to posit a critical peptide length (10 to 17 residues) and a motif for the couplone: two B's at the amino terminus of the peptide, and B-B-X-S or B-B-X-X-B at the carboxy terminus, where S is a basic amino acid (Lys, Arg, or His) and X is any nonbasic amino acid. In another G-coupled receptor, .beta..sub.2 -adrenergic receptor (.beta.2AR), a G.sub.s -activator region termed .beta.III-2 has been identified in the third intracellular loop of .beta.2AR (Okamoto et al., 1991a).